Pre-Pregnancy Vitamin D Intake Reduces Gestational Diabetes Risk

The incidence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM can be responsible for an important proportion of adverse fetal and maternal outcomes during pregnancy. It is important to identify potentially modifiable risk factors for GDM. Accumulating evidence links vitamin D deficiency, defined as serum 25-hydroxyvitamin D level of 75 nmol/L or less, with pregnant women and gestational diabetes. In the United States, vitamin D insufficiency is common among non-pregnant women who are at childbearing age (78%). Sequentially these women may enter pregnancy with suboptimal vitamin D level. Evidence from epidemiological studies has also shown that women who develop GDM are more likely to be vitamin D deficient. However, the number of studies looking at the effect of dietary and supplemental vitamin D on the development of GDM remains unknown. A large prospective cohort study was designed to examine the association of pre-pregnancy intake of dietary and supplemental vitamin D with risk of incident GDM.

Researchers analyzed diet information, including vitamin D intakes from food sources and supplements, from 15,225 women with 21,356 singleton pregnancies between 1991 and 2001 participating in the Nurses’ Health Study II cohort. Information from disease outcomes, lifestyle behaviors and food frequency questionnaires was assessed in 1991 and every 4 years thereafter. Information on current use, doses of vitamin D supplements and vitamin D-containing multivitamins was collected biennially. Researchers used log-binomial models with generalized estimating equations to estimate relative risk for gestational diabetes based on vitamin D intake and 95% confidence intervals. Eligible criteria include pregnancies with no prior GDM, or a prior diagnosis of T2DM, cardiovascular disease, or cancer. Individuals with GDM in a previous pregnancy and/or missing information on vitamin D intake at baseline were not included. Total vitamin D intake was calculated as the sum of dietary and supplemental vitamin D intakes from all sources.

During 10 years of follow-up, 865 gestational diabetes cases were documented among the eligible pregnancies. Researchers found inverse associations between pre-pregnancy supplemental vitamin D intake and the risk of GDM. Participants who reported taking at least 400 IU daily prior to pregnancy were nearly 30% less likely to develop GDM during pregnancy compared with participants who did not take daily supplemental vitamin D before pregnancy (RR = 0.71; 95% CI, 0.56-0.9). Women who took daily vitamin D supplementation between 1 IU and 399 IU also have a reduced risk for developing GDM (RR = 0.8; 95% CI, 0.67-0.96).

These associations remained statistically significant after adjustment for other major risk factors of GDM such as age, parity, race, family history of diabetes, diet and lifestyle factors, and body mass index. The study results also suggested that dietary and total vitamin D intake might be inversely associated with GDM risk, although the associations were not statistically significant.

A recent randomized controlled trial also found a lower rate of GDM (13% vs 8%) after vitamin D supplementation during early pregnancy, although the difference was not statistically significant due to small study samples. Larger randomized controlled trials of pre-pregnancy vitamin D supplementation may be needed to confirm the findings.

This cohort study has several limitations, including a possible misclassification of dietary vitamin D intake; the study population consisted mostly of Caucasian American women; and the cohort did not specifically assess diet and lifestyle factors during pregnancy. Therefore, we were unable to assess the association of pre-pregnancy vitamin D intake with GDM risk, independent of vitamin D intake during pregnancy; and finally, because of the observational nature of this study, a causal relation between pre-pregnancy vitamin D intake and GDM risk cannot be inferred.

Practice Pearls:

Vitamin D insufficiency is common in pregnant women, and it has been associated with gestational diabetes.